Requirement of Zn to demonstrate HCO3-stimulated ATPase activity of rat small intestinal brush border.

The existence of a membrane-bound HCO3-stimulated ATPase in intestinal mucosa is controversial. A crude brush border fraction of rat small intestinal homogenates contained HCO3-ATPase activity which was inhibited by preincubation with 3 mM EDTA. Alkaline phosphatase activity of this preparation was also inhibited in a parallel, time-dependent fashion by preincubation with EDTA. When 5 mM ZnSO4 accompanied 3 mM EDTA in the preincubation mix, preservation of both enzyme activities occurred, demonstrating a requirement of Zn for the activity of both these phosphatases. These studies support the earlier contention that HCO3-ATPase and alkaline phosphatase activities may be different properties of the same enzyme, and raise the possibility that the ATPase could play a role in intestinal ion transport. The failure to identify a membrane-bound HCO3-ATPase by other workers could be due to the exposure of EDTA which occurred in their tissue preparation

Chronic psychosocial and financial burden accelerates 5-year telomere shortening: findings from the Coronary Artery Risk Development in Young Adults Study.

Leukocyte telomere length, a marker of immune system function, is sensitive to exposures such as psychosocial stressors and health-maintaining behaviors. Past research has determined that stress experienced in adulthood is associated with shorter telomere length, but is limited to mostly cross-sectional reports. We test whether repeated reports of chronic psychosocial and financial burden is associated with telomere length change over a 5-year period (years 15 and 20) from 969 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a longitudinal, population-based cohort, ages 18-30 at time of recruitment in 1985. We further examine whether multisystem resiliency, comprised of social connections, health-maintaining behaviors, and psychological resources, mitigates the effects of repeated burden on telomere attrition over 5 years. Our results indicate that adults with high chronic burden do not show decreased telomere length over the 5-year period. However, these effects do vary by level of resiliency, as regression results revealed a significant interaction between chronic burden and multisystem resiliency. For individuals with high repeated chronic burden and low multisystem resiliency (1 SD below the mean), there was a significant 5-year shortening in telomere length, whereas no significant relationships between chronic burden and attrition were evident for those at moderate and higher levels of resiliency. These effects apply similarly across the three components of resiliency. Results imply that interventions should focus on establishing strong social connections, psychological resources, and health-maintaining behaviors when attempting to ameliorate stress-related decline in telomere length among at-risk individuals

Atypical disengagement from faces and its modulation by the control of eye fixation in children with Autism Spectrum Disorder

By using the gap overlap task, we investigated disengagement from faces and objects in children (9–17 years old) with and without autism spectrum disorder (ASD) and its neurophysiological correlates. In typically developing (TD) children, faces elicited larger gap effect, an index of attentional engagement, and larger saccade-related event-related potentials (ERPs), compared to objects. In children with ASD, by contrast, neither gap effect nor ERPs differ between faces and objects. Follow-up experiments demonstrated that instructed fixation on the eyes induces larger gap effect for faces in children with ASD, whereas instructed fixation on the mouth can disrupt larger gap effect in TD children. These results suggest a critical role of eye fixation on attentional engagement to faces in both groups

Impact of Splenectomy on Thrombocytopenia, Chemotherapy, and Survival in Patients with Unresectable Pancreatic Cancer

Patients with unresectable pancreatic cancer (PDAC) or endocrine tumors (PET) often develop splenic vein thrombosis, hypersplenism, and thrombocytopenia which limits the administration of chemotherapy. From 2001 to 2009, 15 patients with recurrent or unresectable PDAC or PET underwent splenectomy for hypersplenism and thrombocytopenia. The clinical variables of this group of patients were analyzed. The overall survival of patients with PDAC was compared to historical controls. Of the 15 total patients, 13 (87%) had PDAC and 2 (13%) had PET. All tumors were either locally advanced (n = 6, 40%) or metastatic (n = 9, 60%). The platelet counts significantly increased after splenectomy (p < 0.01). All patients were able to resume chemotherapy within a median of 11.5 days (range 6–27). The patients with PDAC had a median survival of 20 months (range 4–67) from the time of diagnosis and 10.6 months (range 0.6–39.8) from the time of splenectomy. Splenectomy for patients with unresectable PDAC or PET who developed hypersplenism and thrombocytopenia that limited the administration of chemotherapy, significantly increased platelet counts, and led to resumption of treatment in all patients. Patients with PDAC had better disease-specific survival as compared to historical controls

Hybridization in human evolution: Insights from other organisms

During the late Pleistocene, isolated lineages of hominins exchanged genes thus influencing genomic variation in humans in both the past and present. However, the dynamics of this genetic exchange and associated phenotypic consequences through time remain poorly understood. Gene exchange across divergent lineages can result in myriad outcomes arising from these dynamics and the environmental conditions under which it occurs. Here we draw from our collective research across various organisms, illustrating some of the ways in which gene exchange can structure genomic/phenotypic diversity within/among species. We present a range of examples relevant to questions about the evolution of hominins. These examples are not meant to be exhaustive, but rather illustrative of the diverse evolutionary causes/consequences of hybridization, highlighting potential drivers of human evolution in the context of hybridization including: influences on adaptive evolution, climate change, developmental systems, sex-differences in behavior, Haldane’s rule and the large X-effect, and transgressive phenotypic variation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151330/1/evan21787.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151330/2/evan21787_am.pd

Attentional Prioritization of Infant Faces Is Limited to Own-Race Infants

Background: Recent evidence indicates that infant faces capture attention automatically, presumably to elicit caregiving behavior from adults and leading to greater probability of progeny survival. Elsewhere, evidence demonstrates that people show deficiencies in the processing of other-race relative to own-race faces. We ask whether this other-race effect impacts on attentional attraction to infant faces. Using a dot-probe task to reveal the spatial allocation of attention, we investigate whether other-race infants capture attention. Principal Findings: South Asian and White participants (young adults aged 18–23 years) responded to a probe shape appearing in a location previously occupied by either an infant face or an adult face; across trials, the race (South Asian/ White) of the faces was manipulated. Results indicated that participants were faster to respond to probes that appeared in the same location as infant faces than adult faces, but only on own-race trials. Conclusions/Significance: Own-race infant faces attract attention, but other-race infant faces do not. Sensitivity to facespecific care-seeking cues in other-race kindenschema may be constrained by interracial contact and experience

Using Routinely Collected Administrative Data in Public Health Research: Geocoding Alcohol Outlet Data

We describe our process of geocoding alcohol outlets to create a national longitudinal exposure dataset for Wales, United Kingdom from 2006 to 2011. We investigated variation in the availability of data items and the quality of alcohol outlet addresses held within unitary authorities. We used a standard geocoding method augmented with a manual matching procedure to achieve a fully spatially referenced dataset. We found higher quality addresses are held for outlets based in urban areas, resulting in the automatic geocoding of 68 % of urban outlets, compared to 48 % in rural areas. Missing postcodes and a lack of address structure contributed to a lower geocoding proportion. An urban rural bias was removed with the development of a manual matching procedure. Only one-half of the unitary authorities provided data on on/off sales and opening times, which are important availability factors. The resulting outlet dataset is suitable for contributing to the evidence-base of alcohol availability and alcohol-related harm. Local government should be encouraged to use standardised data fields, including addresses, to enable accurate geocoding of alcohol outlets and facilitate research that aims to prevent alcohol-related harm. Standardising data collection would enable efficient secondary data reuse using record linkage techniques, allowing the retrospective creation and evaluation of population-based natural experiments to provide evidence for policy and practice

The sensitivity and specificity of four questions (HARK) to identify intimate partner violence: a diagnostic accuracy study in general practice

<p>Abstract</p> <p>Background</p> <p>Intimate partner violence (IPV) including physical, sexual and emotional violence, causes short and long term ill-health. Brief questions that reliably identify women experiencing IPV who present in clinical settings are a pre-requisite for an appropriate response from health services to this substantial public health problem. We estimated the sensitivity and specificity of four questions (HARK) developed from the Abuse Assessment screen, compared to a 30-item abuse questionnaire, the Composite Abuse Scale (CAS).</p> <p>Methods</p> <p>We administered the four HARK questions and the CAS to women approached by two researchers in general practice waiting rooms in Newham, east London. Inclusions: women aged more than 17 years waiting to see a doctor or nurse, who had been in an intimate relationship in the last year. Exclusions: women who were accompanied by children over four years of age or another adult, too unwell to complete the questionnaires, unable to understand English or unable to give informed consent.</p> <p>Results</p> <p>Two hundred and thirty two women were recruited. The response rate was 54%. The prevalence of current intimate partner violence, within the last 12 months, using the CAS cut off score of ≥3, was 23% (95% C.I. 17% to 28%) with pre-test odds of 0.3 (95% C.I. 0.2 to 0.4). The receiver operator characteristic curve demonstrated that a HARK cut off score of ≥1 maximises the true positives whilst minimising the false positives. The sensitivity of the optimal HARK cut-off score of ≥1 was 81% (95% C.I. 69% to 90%), specificity 95% (95% C.I. 91% to 98%), positive predictive value 83% (95% C.I. 70% to 91%), negative predictive value 94% (95% C.I. 90% to 97%), likelihood ratio 16 (95% C.I. 8 to 31) and post-test odds 5.</p> <p>Conclusion</p> <p>The four HARK questions accurately identify women experiencing IPV in the past year and may help women disclose abuse in general practice. The HARK questions could be incorporated into the electronic medical record in primary care to prompt clinicians to ask about recent partner violence and to encourage disclosure by patients. Future research should test the effectiveness of HARK in clinical consultations.</p

Manipulable Objects Facilitate Cross-Modal Integration in Peripersonal Space

Previous studies have shown that tool use often modifies one's peripersonal space – i.e. the space directly surrounding our body. Given our profound experience with manipulable objects (e.g. a toothbrush, a comb or a teapot) in the present study we hypothesized that the observation of pictures representing manipulable objects would result in a remapping of peripersonal space as well. Subjects were required to report the location of vibrotactile stimuli delivered to the right hand, while ignoring visual distractors superimposed on pictures representing everyday objects. Pictures could represent objects that were of high manipulability (e.g. a cell phone), medium manipulability (e.g. a soap dispenser) and low manipulability (e.g. a computer screen). In the first experiment, when subjects attended to the action associated with the objects, a strong cross-modal congruency effect (CCE) was observed for pictures representing medium and high manipulability objects, reflected in faster reaction times if the vibrotactile stimulus and the visual distractor were in the same location, whereas no CCE was observed for low manipulability objects. This finding was replicated in a second experiment in which subjects attended to the visual properties of the objects. These findings suggest that the observation of manipulable objects facilitates cross-modal integration in peripersonal space

Protective Effector Memory CD4 T Cells Depend on ICOS for Survival

Memory CD4 T cells play a vital role in protection against re-infection by pathogens as diverse as helminthes or influenza viruses. Inducible costimulator (ICOS) is highly expressed on memory CD4 T cells and has been shown to augment proliferation and survival of activated CD4 T cells. However, the role of ICOS costimulation on the development and maintenance of memory CD4 T cells remains controversial. Herein, we describe a significant defect in the number of effector memory (EM) phenotype cells in ICOS−/− and ICOSL−/− mice that becomes progressively more dramatic as the mice age. This decrease was not due to a defect in the homeostatic proliferation of EM phenotype CD4 T cells in ICOS−/− or ICOSL−/− mice. To determine whether ICOS regulated the development or survival of EM CD4 T cells, we utilized an adoptive transfer model. We found no defect in development of EM CD4 T cells, but long-term survival of ICOS−/− EM CD4 T cells was significantly compromised compared to wild-type cells. The defect in survival was specific to EM cells as the central memory (CM) ICOS−/− CD4 T cells persisted as well as wild type cells. To determine the physiological consequences of a specific defect in EM CD4 T cells, wild-type and ICOS−/− mice were infected with influenza virus. ICOS−/− mice developed significantly fewer influenza-specific EM CD4 T cells and were more susceptible to re-infection than wild-type mice. Collectively, our findings demonstrate a role for ICOS costimulation in the maintenance of EM but not CM CD4 T cells